The NALP3 inflammasome is involved in the innate immune response to amyloid-β

A Halle, V Hornung, GC Petzold, CR Stewart… - Nature …, 2008 - nature.com
A Halle, V Hornung, GC Petzold, CR Stewart, BG Monks, T Reinheckel, KA Fitzgerald, E Latz
Nature immunology, 2008nature.com
The fibrillar peptide amyloid-β (Aβ) has a chief function in the pathogenesis of Alzheimer's
disease. Interleukin 1β (IL-1β) is a key cytokine in the inflammatory response to Aβ.
Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic
receptor NALP3, which results in the release of IL-1β. Here we identify the NALP3
inflammasome as a sensor of Aβ in a process involving the phagocytosis of Aβ and
subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1β pathway …
Abstract
The fibrillar peptide amyloid-β (Aβ) has a chief function in the pathogenesis of Alzheimer's disease. Interleukin 1β (IL-1β) is a key cytokine in the inflammatory response to Aβ. Insoluble materials such as crystals activate the inflammasome formed by the cytoplasmic receptor NALP3, which results in the release of IL-1β. Here we identify the NALP3 inflammasome as a sensor of Aβ in a process involving the phagocytosis of Aβ and subsequent lysosomal damage and release of cathepsin B. Furthermore, the IL-1β pathway was essential for the microglial synthesis of proinflammatory and neurotoxic factors, and the inflammasome, caspase-1 and IL-1β were critical for the recruitment of microglia to exogenous Aβ in the brain. Our findings suggest that activation of the NALP3 inflammasome is important for inflammation and tissue damage in Alzheimer's disease.
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